712-30-1Relevant articles and documents
Generation of Reactive Oxygen Species during the Photolysis of 6-(Hydroxymethyl)pterin in Alkaline Aqueous Solutions
Cabrerizo, Franco M.,Thomas, Andres H.,Lorente, Carolina,Dantola, Maria L.,Petroselli, Gabriela,Erra-Balsells, Rosa,Capparelli, Alberto L.
, p. 349 - 365 (2004)
Photochemical studies of the reactivity of 6-(hydroxymethyl)pterin (=2-amino-6-(hydroxymethyl)pteridin-4(1H)-one; HPT) in alkaline aqueous solutions (pH 10.2-10.8) at 350 nm and room temperature were performed. The photochemical reactions were followed by UV/VIS spectrophotometry, thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and an enzymatic method for H2O2 determination. In the presence of O2, 6-formylpterin (=2-amino-3,4-dihydro-4-oxopteridine-6-carboxaldehyde; FPT) was the only photoproduct detected. In the absence of O2, we observed a compound with an absorbance maximum at 480 nm, which was oxidized very rapidly by O 2 in a dark reaction to yield FPT. The quantum yields of substrates disappearance and of photoproducts formation were determined. The formation of H2O2 during photooxidation was monitored, and the number of mol of H2O2 released per mol of HPT consumed corresponded to a 1: 1 stoichiometry. HPT was also investigated for efficiency of singlet-oxygen (1O2) production and quenching in aqueous solution. The quantum yield of 1O2 production (ΦΔ = 0.21 ± 0.01) was determined by measurements of the 1O2 luminescence in the near-IR (1270 nm) upon continuous excitation of the sensitizer. The rate constant of 1O 2 total quenching by HPT was determined (kt = 3.1 · 106 M-1 s-1), indicating that this compound was able to quench 1O2. However, 1O2 did not participate in the photooxidation of HPT to FPT.
Photoinduced formation of reactive oxygen species from the acid form of 6-(hydroxymethyl)pterin in aqueous solution
Thomas, Andres H.,Cabrerizo, Romina,Vignoni, Mariana,Erra-Balsells, Rosa,Cabrerizo, Franco M.,Capparelli, Alberto L.
, p. 1090 - 1104 (2006)
The photochemistry of 6-(hydroxymethyl)pterin (HPT; 1) in aqueous solution (pH 5-6) was investigated by irradiation at 350 nm at room temperature. The photochemical reactions of the acidic form 1a were followed by UV/VIS spectrophotometry, thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and enzymatic methods for the determination of the superoxide anion radical (O2.-) and hydrogen peroxide (H2O2). When 1a is exposed to UV-A radiation, the intermediates 4 and 4′ are formed reacting with O2 to yield 6-formylpterin (FPT; 5) and 6-carboxypterin (CPT; 6). under formation of O 2.- and H2O2 (Scheme 3). The quantum yields of the disappearance of HPT (1a) and of the formation of the photoproducts 5 and 6 were determined. HPT was investigated for its efficiency in singlet-oxygen (1O2) production in acidic aqueous solution. The corresponding quantum yield of 1O2 production (ΦΔ) was 0.15±0.02, as measured by the 1O2 luminescence in the near-IR (1270 nm) upon continuous excitation of the sensitizer. However, 1O2 does not participate in the actual photooxidation of HPT (1a) to FPT (5) and CPT (6).
Visible-light photochemistry of 6-formyl-7,8-dihydropterin in aqueous solution
Dántola, M. Laura,Thomas, Andrés H.,Oliveros, Esther,Lorente, Carolina
, p. 104 - 110 (2010)
Pterins are a family of heterocyclic compounds present in a wide range of living systems and are involved in different photobiological processes. 6-Formyl-7,8-dihydropterin (H2Fop), is a product of oxidation of several natural occurring pterin derivatives, and its absorption spectrum presents as special feature an intense band in the visible region. Studies of the photochemistry of H2Fop in aqueous solutions under visible radiation and room temperature were performed. The photochemical reactions were followed by UV-vis spectrophotometry, electrochemical measurement of dissolved O2, enzymatic methods for H2O2 determination and HPLC. When H2Fop in air-equilibrated solution was exposed to light, O2 was consumed, the reactant was oxidized to 6-formylpterin (Fop), and H2O2 released. When the photolysis took place in the absence of O2, a red compound was generated. This product was rapidly oxidized to Fop on admission of O2. The quantum yields of H2Fop disappearance and of photoproducts formation are reported and the effect of pH is analyzed. The potential biological implications of the results obtained are also discussed.
Unexpected photoactivation pathways in a folate-receptor-targetedtrans-diazido Pt(iv) anticancer pro-drug
Gandioso, Albert,Marchán, Vicente,Rovira, Anna,Sadler, Peter J.,Shi, Huayun
supporting information, p. 11828 - 11834 (2020/09/21)
A conjugate between a photoactivetrans-diazido Pt(iv) pro-drug,trans,trans,trans-[Pt(N3)2(OH)2(py)2], and folic acid has been synthesized and fully characterized by high resolution ESI-MS, NMR and UV-vis spectroscopy. Photoactivation of the Pt-folate conjugate with visible light confirmed the generation of cytotoxic Pt(ii) species capable of binding to guanine nucleobases. Importantly, photoreduction of the Pt(iv) complex triggered the photodecomposition of the folate vector into ap-aminobenzoate-containing fragment and several pterin derivatives, including 6-formylpterin. Besides exhibiting high dark stability in physiological-like conditions, the Pt-folate conjugate wasca. 2× more photocytotoxic towards MCF-7 breast cancer cell line than its parent Pt(iv) complex with a high photoselectivity index (PI > 6.9). The higher photocytotoxicity of the conjugate may be a consequence of its higher cellular accumulation and of the generation of a set of different cytotoxic species, including Pt(ii) photoproducts and several pterin derivatives, which are known to generate ROS.
Effect of pterin impurities on the fluorescence and photochemistry of commercial folic acid
Dántola, M. Laura,Urrutia, M. Noel,Thomas, Andrés H.
, p. 157 - 163 (2018/03/24)
Folic acid, or pteroyl?L?glutamic acid (PteGlu) is a conjugated pterin derivative that is used in dietary supplementation as a source of folates, a group of compounds essential for a variety of physiological functions in humans. Photochemistry of PteGlu is important because folates are not synthesized by mammals, undergo photodegradation and their deficiency is related to many diseases. We have demonstrated that usual commercial PteGlu is unpurified with the unconjugated oxidized pterins 6?formylpterin (Fop) and 6?carboxypterin (Cap). These compounds are in such low amounts that a normal chromatographic control would not detect any pterinic contamination. However, the fluorescence of PteGlu solutions is due to the emission of Fop and Cap and the contribution of the PteGlu emission, much lower, is negligible. This is because the fluorescence quantum yield (ΦF) of PteGlu is extremely weak compared to the ΦF of Fop and Cap. Likewise, the PteGlu photodegradation upon UV-A radiation is an oxidation photosensitized by oxidized unconjugated pterins present in the solution, and not a process initiated by the direct absorption of photons by PteGlu. In brief, the fluorescence and photochemical properties of PteGlu solutions, prepared using commercially available solids, are due to their unconjugated pterins impurities and not to PteGlu itself. This fact calls into question many reported studies on fluorescence and photooxidation of this compound.
Synthesis and analysis of bacterial folate metabolism intermediates and antifolates
Dawadi, Surendra,Kordus, Shannon L.,Baughn, Anthony D.,Aldrich, Courtney C.
, p. 5220 - 5223 (2017/11/06)
The mechanism of action of para-aminosalicylic acid (PAS), a drug used to treat drug-resistant tuberculosis (TB), has been confirmed through the first synthesis and biochemical characterization of its active metabolite 7. The synthesis features the coupling of N2-acetyl-6-formylpterin obtained from the degradation of folic acid and appropriately functionalized arylamines to form Schiff bases. The sequential chemoselective reduction of the imine and pterin ring led to the formation of dihydrofolate analogue 7 and two other dihydropteroate species.
Photoinactivation of tyrosinase sensitized by folic acid photoproducts
Laura Dántola,Zurbano, Beatriz N.,Thomas, Andrés H.
, p. 172 - 179 (2015/06/25)
Tyrosinase catalyzes in mammals the first and rate-limiting step in the biosynthesis of the melanin, the main pigment of the skin. Pterins, heterocyclic compounds able to photoinduce oxidation of biomolecules, accumulate in the skin of patients suffering from vitiligo, where there is a lack of melanin. Folic acid (PteGlu) is a conjugated pterin widespread in biological systems. Aqueous solutions of tyrosinase were exposed to UV-A irradiation (350 nm) in the presence of PteGlu and its photoproducts (6-formylpterin and 6-carboxypterin). The reactions were followed by UV-Vis spectrophotometry, enzyme activity measurement, fluorescence spectroscopy and HPLC. In this work, we present data that demonstrate unequivocally that solutions of tyrosinase exposed to UV-A irradiation in the presence of PteGlu, undergo enzyme inactivation. However, PteGlu itself causes a negligible effect on the activity of the enzyme. In contrast, PteGlu photoproducts are efficient photosensitizers. The tyrosinase inactivation involves two different pathways: (i) a photosensitization process and (ii) the oxidation of the enzyme by the hydrogen peroxide produced during the photooxidation of PteGlu and its photoproduct. The former pathway affects both the active site and the tryptophan residues, whereas the latter affects only the active site. The biological implications of the results are discussed.
Photochemistry of dihydrobiopterin in aqueous solution
Vignoni, Mariana,Cabrerizo, Franco M.,Lorente, Carolina,Claparols, Catherine,Oliveros, Esther,Thomas, Andres H.
experimental part, p. 800 - 810 (2010/06/20)
Dihydrobiopterin (H2Bip) and its oxidized analogue, biopterin (Bip), accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder in which the protection against UV radiation fails. The photochemistry of H2Bip was studied in neutral aqueous solutions upon UV-A irradiation (320-400 nm) at room temperature. The photochemical reactions were followed by UV/vis spectrophotometry, HPLC and enzymatic methods for hydrogen peroxide (H2O2) determination. Photoproducts were analyzed by means of electrospray ionization mass spectrometry. Under anaerobic conditions, excitation of H2Bip leads to the formation of at least two isomeric dimers with molecular masses equal to exactly twice the molecular mass of the reactant. This reaction takes place from the singlet excited state of the reactant. To the best of our knowledge, this is the first time that the photodimerization of a dihydropterin is reported. In the presence of air, the dimers are again the main photoproducts at the beginning of the reaction, but a small proportion of the reactant is converted into Bip. As the reaction proceeds and enough Bip accumulates in the solution, a photosensitized process starts, where Bip photoinduces the oxidation of H2Bip to Bip, and H 2O2 is formed. As a consequence, the rates of H 2Bip consumption and Bip formation increase as a function of irradiation time, resulting in an autocatalytic photochemical process. In this process, Bip in its triplet excited state reacts with the ground state of H 2Bip. The mechanisms involved are analyzed and the biological implications of the results are discussed. The Royal Society of Chemistry 2010.
New results on the photochemistry of biopterin and neopterin in aqueous solution
Vignoni, Mariana,Cabrerizo, Franco M.,Lorente, Carolina,Thomas, Andres H.
body text, p. 365 - 373 (2009/04/18)
New photochemical studies of the reactivity of biopterin (BPT) and neopterin (NPT) in acidic (pH = 5.5) and alkaline (pH = 10.5) aqueous solutions at 350 nm and room temperature were performed. The photochemical properties of BPT are of particular interes
Reactivity of conjugated and unconjugated pterins with singlet oxygen (O2(1Δg)): Physical quenching and chemical reaction
Cabrerizo, Franco M.,Laura Dantola,Petroselli, Gabriela,Capparelli, Alberto L.,Thomas, Andres H.,Braun, Andre M.,Lorente, Carolina,Oliveros, Esther
, p. 526 - 534 (2008/03/14)
Pterins (PTs) belong to a class of heterocyclic compounds present in a wide range of living systems. They participate in relevant biological functions and are involved in different photobiological processes. We have investigated the reactivity of conjugated PTs (folic acid [FA], 10-methylfolic acid [MFA], pteroic acid [PA]) and unconjugated PTs (PT, 6-hydroxymethylpterin [HPT], 6-methylpterin [MPT], 6,7-dimethylpterin [DPT], rhamnopterin [RPT]) with singlet oxygen (1O2) in aqueous solutions, and compared the efficiencies of chemical reaction and physical quenching. The chemical reactions between 1O2, produced by photosensitization, and PT derivatives were followed by UV-visible spectrophotometry and high-performance liquid chromatography, and corresponding rate constants (kr) were evaluated. Whenever possible, products were identified and quantified. Rate constants of 1O2 total quenching by the PT derivatives investigated were obtained from steady-state 1O2 luminescence measurements. Results show that the behavior of conjugated PTs differs considerably from that of unconjugated derivatives, and the mechanisms of 1O2 physical quenching by these compounds and of their chemical reaction with 1O2 are discussed in relation to their structural features.
